OBJECTIVE:. The objective of this project is to develop successful clinical strategies for the early detection and treatment of esophageal cancer. BACKGROUND: Esophageal cancer has a very poor prognosis, primarily because most tumors produce symptoms only after they have spread beyond the esophageal wall and are unresectable. Significant improvement in survival will require successful strategies to diagnose and treat more cases at earlier, more curable stages of the disease. METHODS: The project includes five studies: the Cytology Sampling Study (CSS), the Mucosal Staining Study (MSS), the Endoscopic Staging Study (ESS), the Endoscopic Therapy Pilot Study (ETPS), and the Chemoregression Study (CRS), each designed to evaluate a technique that may be useful in a practical early detection and treatment program. The project is being carried out in Linxian, China, a county with very high rates of esophageal cancer. PROGRESS: In the past year, field work and primary analysis were completed in the CRS. This study randomized 360 patients with biopsy-proven mild or moderate squamous dysplasia (a precursor lesion for esophageal squamous cell carcinoma) to one of four treatment groups, taking oral doses of selenomethionine 200 ug once a day, celecoxib 200 mg twice a day, both medications, or neither. Endoscopy with mucosal iodine staining and biopsy of all unstained areas > 5mm was performed at baseline (T0) and after ten months of intervention (T10). During the intervention, village doctors monitored the patients daily for pill compliance and adverse events. At T10, 313 (87%) of the patients were endoscoped and biopsied again with the same protocol. The primary endpoint of the trial was the change in each subject's worst histologic diagnosis between T0 and T10 (regression/stable disease/progression), tested by a two-sample permutation t-test. Analysis of the analytic cohort (n=238) showed that celecoxib was not associated with a significant change in dysplasia severity (p=0.78). Selenomethionine had no apparent effect in subjects with moderate dysplasia at baseline (p=1.00), but showed a significant improvement in dysplasia severity in subjects with a baseline diagnosis of mild dysplasia (p=0.02). Based on these data, further investigation of selenomethionine as a potential chemoprevention agent for esophageal squamous cell carcinoma appears warranted.